A5047967464- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- MicroRNA in disease regulation
- Cellular transport and secretion
- Fibroblast Growth Factor Research
- Synthesis and biological activity
- RNA regulation and disease
- Protein Tyrosine Phosphatases
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Cancer-related molecular mechanisms research
- Melanoma and MAPK Pathways
- Enzyme Structure and Function
Institute of Structural and Molecular Biology
2023
University of Leeds
2019-2023
University of Nottingham
2018-2020
The recruitment of signaling proteins into activated receptor tyrosine kinases (RTKs) to produce rapid, high-fidelity downstream response is exposed the ambiguity random diffusion target site. Liquid-liquid phase separation (LLPS) overcomes this by providing elevated, localized concentrations required while impeding competitor ligands. Here, we show a subset phosphorylation-dependent RTK-mediated LLPS states. We then investigate formation phase-separated droplets comprising ternary complex...
Abstract Cell biologists generally consider that microtubules and actin play complementary roles in long- short-distance transport animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered motor protein myosin-Va works with dynamic tracks to drive long-range organelle dispersion opposition microtubules. This suggests animals, yeast plants, myosin/actin can transport. Here, show SPIRE-type nucleators (predominantly SPIRE1) are Rab27a effectors...
Receptor tyrosine kinase (RTK)-mediated hyperactivation of the MAPK/Erk pathway is responsible for a large number pathogenic outcomes including many cancers. Considerable effort has been directed at targeting this with varying degrees long term therapeutic success. Under non-stimulated conditions Erk bound to adaptor protein Shc preventing aberrant signalling by sequestering from activation Mek. Activated RTK recruits Shc, via its phosphotyrosine binding (PTB) domain (ShcPTB), precipitating...
Activation of RAS is crucial in driving cellular outcomes including proliferation, differentiation, migration and apoptosis via the MAPK pathway. This initiated on recruitment Grb2, as part a Grb2-Sos complex, to an up-regulated receptor tyrosine kinase (RTK), enabling subsequent interaction Sos with plasma membrane-localised RAS. Aberrant regulation at this convergence point for RTKs signalling key driver multiple cancers. Splicing GRB2 gene produces deletion variant, Grb3-3, that incapable...
Protein interactions with the microRNA (miRNA)-mediated gene silencing protein Argonaute 2 (AGO2) control miRNA expression. biogenesis starts production of precursor transcripts and culminates loading mature onto AGO2 by DICER1. Here we reveal an additional component to regulatory mechanism for involving adaptor protein, growth factor receptor-bound (GRB2). The N-terminal SH3 domain GRB2 is recruited PAZ forming a ternary complex containing GRB2, Using small-RNA sequencing identified two...
Abstract Cell biologists generally consider that microtubules and actin play complementary roles in long- short-distance transport animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered motor myosin-Va, works with dynamic tracks, to drive long-range organelle dispersion microtubule depleted This suggests animals, yeast plants, myosin/actin can transport. Here show SPIRE1/2 formin-1 (FMN1) proteins generate tracks required for myosin-Va-dependent...
Receptor tyrosine kinases (RTKs), the largest class of transmembrane cell surface receptors, initiate signalling pathways which regulate diverse cellular processes. On activation these receptors rapidly recruit multiple downstream effector proteins to moderate affinity tyrosyl phosphate (pY) binding sites. However, mechanism for expedient protein recruitment via random molecular diffusion through cytoplasm is not fully understood. One way in probabilistic outcome associated with could be...